During 1978 and 1979, outbreaks of previously unrecognized disease were observed in dogs in a number of countries. Identification of the causative agent, canine parvovirus (CPV), was made when comparisons between the disease seen in dogs and those caused in cats by feline panleukopenia virus (FPV) or in minks by mink enteritis virus (MEV), both parvoviruses, were noted. CPV has become endemic in domestic and wild dog populations around the world. Rapid global spread of the virus was most likely due to the high viral titers found in feces of infected dogs (Parrish, C. R., Adv. Virus Res. 38:403-450, 1990).
Two clinical conditions are recognized--enteric disease in pups older than 4 to 5 weeks, and myocardial disease in pups 3 to 16 weeks old. CPV is responsible for serious illness and mortality in dogs, and pups less than 6 months old are particularly susceptible (Carmichael et al., Cornell Vet. 73:13-29, 1983).
Canine parvovirus (CPV) is an autonomous parvovirus with a DNA genome of about 5,000 bases of single-stranded DNA. Two structural genes are characterized (VP-1 and VP-2), as well as one or two non-structural (NS) genes (Parrish et al. J. Virol, 65:6544-6552, 1991).
The original strain of CPV (CPV-2), first identified in 1978, was almost completely replaced between 1979 and 1982 by an antigenic and genetic variant, CPV-2a. A later antigenic variant, CPV-2b, emerged around 1984 and became the predominant virus type by 1988. It has largely replaced the previous strains in the United States, such that over 90% of infected dogs now carry this strain. DNA sequence analysis shows that sequence variation in the VP1/VP2 genes gave rise to successive antigenic virus types, such that the CPV-2a strain differed in only 5 or 6 amino acids from CPV-2, while CPV-2b differs in only 2 amino acids from CPV-2a (Parrish et al. J. Virol 65:6544-6552, 1991).
Vaccines designed to elicit protection against previous strains of CPV have been developed, including live (U.S. Pat. No. 4,303,645 dated Dec. 1, 1981; U.S. Pat. No. 4,810,494 dated Mar. 7, 1989) inactivated (U.S. Pat. No. 4,193,991 dated Mar. 18, 1980), heterotypic (U.S. Pat. No. 4,193,990 dated Mar. 18, 1980) as well as recombinant subunit vaccines (U.S. Pat. No. 4,971,793 dated Nov. 20, 1990; Lopez de Turiso et al., J. Virol. 66:2748-2753, 1992). Baculovirus expression of the CPV capsid genes generated empty parvoviral capsids which could be used to immunize dogs against challenge with CPV-2b (Mazzara et al., Vaccines' 87, Cold Spring Harbor Laboratory Press, 1987, p. 419-424; Saliki et al., J. Gen. Virol. 73:369-374, 1992).
The advantage of a vaccine derived from an attenuated virus over a heterotypic, inactivated, or recombinant vaccine is that the virus is able to reproduce in the host system such that an immune response is maintained over time.
Until the invention described herein, no attenuated vaccines have been developed which are derived from the most recent CPV-2b strain that is the most prevalent form of the virus found in infected dogs.
Citation or identification of any of the references in Section 2 of this application shall not be construed as an admission that such reference is available as prior art to the present invention.